Atypical Presentations of ADEM in Older Adults
ADEM in older adults frequently presents with atypical features that diverge from classic pediatric presentations, including prominent psychiatric symptoms, symmetric white matter involvement without clear infectious triggers, prolonged vegetative states, and imaging patterns that mimic stroke, tumor, or infection rather than typical demyelinating disease.
Key Atypical Clinical Features
Neuropsychiatric Manifestations
Older adults with ADEM commonly present with behavioral changes, mutism, psychosis, and acute confusional states rather than the typical encephalopathy seen in children 1. These psychiatric symptoms may be severe enough to warrant initial admission to psychiatric wards, delaying appropriate diagnosis and treatment 1. One case series specifically noted that acute or subacute onset psychosis in adults with recent travel history should raise suspicion for ADEM 1.
Prolonged Encephalopathy and Vegetative States
Unlike pediatric cases, elderly patients may experience extended periods of severe encephalopathy, including persistent vegetative states lasting weeks 2. One documented case showed a 69-year-old woman who remained vegetative for 39 days without response to high-dose corticosteroids, only improving after IVIG therapy 2. This prolonged unresponsiveness is highly atypical for classic ADEM and creates diagnostic uncertainty.
Absence of Infectious Triggers
While pediatric ADEM typically follows identifiable infections or vaccinations, older adults frequently present without obvious preceding infectious illness 1. Cases have been reported following surgical procedures (such as prostate resection) 3, or with no identifiable trigger whatsoever 4. This absence of classic prodromal events complicates diagnosis and challenges traditional diagnostic criteria.
Atypical Neuroimaging Patterns
Symmetric White Matter Involvement
Elderly ADEM patients may show bilateral, symmetric T2/FLAIR hyperintensities in subcortical white matter, which differs from the typical asymmetric, multifocal pattern 2. One case demonstrated symmetric involvement of the middle cerebellar peduncles with pontine and periventricular extension 4, a pattern more suggestive of metabolic or toxic processes than classic demyelination.
Mimicry of Other Pathologies
Imaging in older adults frequently suggests alternative diagnoses:
- Contrast-enhancing lesions mimicking metastases or primary CNS tumors 5
- Restricted diffusion on DWI suggesting acute stroke 5
- Posterior-predominant semi-confluent lesions that may be confused with posterior reversible encephalopathy syndrome 3
These atypical imaging features often necessitate tissue diagnosis, as two patients in one series required brain biopsy for conclusive diagnosis 5.
Diagnostic Challenges and Red Flags
Laboratory Findings
Oligoclonal bands are frequently negative in elderly ADEM patients 5, unlike multiple sclerosis. CSF may show only mild protein elevation without significant pleocytosis 3, or even normal findings when sampled early 2. This contrasts with pediatric cases where CSF pleocytosis is more common.
MOG-IgG Testing Considerations
Based on international guidelines, MOG-IgG testing should be considered in older adults presenting with ADEM-like features, particularly those with:
- Large white matter lesions with disturbance of consciousness
- Brainstem involvement
- Extensive spinal cord involvement
- Steroid-dependent or recurrent symptoms 6
However, MOG-IgG may be negative or transiently disappear in monophasic adult ADEM cases 6, and timing of testing relative to disease activity and treatment affects results.
Clinical Course and Prognosis
Poor Prognostic Features
The prognosis in elderly ADEM patients is significantly less favorable than in pediatric cases 7. Two elderly Filipino patients with adult-onset ADEM experienced disease progression despite treatment with high-dose steroids, IVIG, and plasma exchange, ultimately succumbing five months after illness onset 7.
Delayed Treatment Response
Older adults may show delayed or incomplete response to standard immunotherapy 2. Some cases demonstrate spontaneous improvement weeks after presentation 4, while others require escalation from steroids to IVIG or plasma exchange before showing neurological recovery 2.
Motor and Cognitive Sequelae
When recovery occurs, it may be incomplete. Patients may progress from hemiplegia to residual weakness (4/5 strength) 4, and the risk of permanent neurological impairment appears higher than in younger populations.
Critical Diagnostic Pitfalls
Dismissing psychiatric symptoms as primary psychiatric illness rather than recognizing them as manifestations of CNS inflammation 1
Pursuing oncological workup for enhancing lesions without considering inflammatory demyelination 5
Attributing symmetric white matter changes to small vessel disease in patients with vascular risk factors 2
Delaying immunotherapy while awaiting definitive diagnosis, when early treatment may be critical despite diagnostic uncertainty 3
Assuming negative OCBs exclude demyelinating disease - this is typical in elderly ADEM 5
Treatment Implications
Given the atypical presentations and poorer outcomes in elderly patients, aggressive early immunosuppression is warranted even when diagnosis remains uncertain 3, 7. The treatment sequence typically involves:
- High-dose methylprednisolone as first-line therapy
- IVIG for steroid-refractory cases 2
- Plasma exchange for severe or progressive disease 7
Tissue diagnosis through brain biopsy may be necessary when imaging mimics neoplastic or vascular disease and clinical response to empiric immunotherapy is unclear 5. Pathological findings showing perivascular myelin loss with relative axonal sparing confirm the diagnosis 5.
The rarity of ADEM in older adults, combined with these atypical features, means clinicians must maintain high diagnostic suspicion and low threshold for empiric immunotherapy in elderly patients presenting with acute encephalopathy and multifocal white matter lesions, even without classic infectious prodrome or typical imaging patterns.